Conserved β-tubulin as a target of ivermectin in plant-parasitic nematodes: molecular modelling and experimental protection of potato

Ivermectin (IVM), a widely used antiparasitic drug, primarily targets glutamate-gated chloride channels; however, it has also been shown to interact with β-tubulin, suggesting an additional mechanism of action. Our study aimed to evaluate the conservation of β-tubulin among plant-parasitic nematodes and computationally assess the ability of IVM to form stable complexes with this protein. We also examined its protective effect on potato ( Solanum tuberosum ) plants during phytonematode infection. Comparative sequence analysis revealed a high degree of β-tubulin conservation among plant-parasitic nematodes (average sequence identity of 91%), particularly within the taxane-binding site. In contrast, significant divergence was observed in potato β-tubulin. Based on the results of molecular docking and molecular dynamics simulations it was predicted that IVM can form stable complexes with β-tubulin from multiple plant-parasitic nematodes, with binding energies ranging from − 6.01 to − 17.83 kcal mol −1 , substantially stronger than the interaction predicted for S. tuberosum β-tubulin (− 3.77 kcal mol⁻ 1 ). Key interactions involved the benzofuran and macrocyclic regions of IVM within the taxane moiety, whereas the disaccharide moiety adversely affected complex stability. In vivo experiments showed that IVM at concentrations of 10–50 μg.mL⁻ 1 had protective effect on S. tuberosum under the nematode co-infestation , significantly reducing cyst, egg, and larval counts and mitigating negative impact of nematodes on S. tuberosum growth and development. Our results show that β-tubulin is a highly conserved and functionally significant, computationally predicted target of IVM in plant-parasitic nematodes, laying the foundation for further experimental validation. The stronger interaction of IVM with nematode β-tubulin compared to potato β-tubulin, together with its inhibitory effects on nematodes, highlights the potential of IVM as a promising tool for controlling phytonematode infections and protecting plants. Furthermore, the identified structural groups of IVM binding can be used for the rational design and virtual screening of new nematicidal compounds targeting β-tubulin. Overall, these findings advance our understanding of IVM mode of action and open new opportunities for the development of sustainable strategies to control plant-parasitic nematodes.